This edition of HATIP was kindly supported by the Stop TB department of the World Health Organization and the Diana, Princess of Wales Memorial Fund.

Key points

Assess,
advise, agree, assist, and arrange. Find out about the patient and their life
in order to create the best possible conditions for adherence.

Empiric
treatment (starting treatment before the results of a drug susceptibility
tests are available) should be approached with caution in cases of
treatment failure. Only a minority of first-line TB patients who
deteriorate have MDR-TB.

Second-line
TB treatment should consist of at least four drugs including an injectable
agent and two other agents, lasting for at least six months, followed by a
further 12-18 months treatment without the injectable drugs.

Moxifloxacin
may be a useful drug for MDR-TB treatment, but is very expensive and few
clinics have access to it. Greater advocacy is needed to bring down the
price and increase access.

Active
monitoring of side-effects is important and all clinical staff attending
the patient with MDR-TB should be aware of the major side-effects of all
second-line drugs. These are nausea, vomiting, diarrhoea and skin
reactions.

Gastrointestinal
problems are the main reason why patients stop MDR-TB treatment, so they
need to be managed.

Hypokalaemia
(low potassium levels) leads to cramps, dizziness, numbness and confusion.
It is a common side-effect of the injectable drugs, may be
life-threatening if severe, and can be treated with potassium and
magnesium supplements.

TB
and HIV drugs can cause peripheral neuropathy (nerve damage in the limbs).
Make sure the patient is taking pyridoxine.

Observe
patients carefully for hearing loss, a side-effect of the injectable drug
kanamycin.

End-of-life
care for patients whose TB does not respond to treatment requires
consideration of whether to stop TB treatment, and where individuals
should receive end-of-life care.

Dyspnoea
(severe breathlessness) is likely to have the greatest impact on quality
of life at this time. It can be managed with low-dose opiates.

Introduction

This HATIP looks at the sequence of care of a person with, or suspected
of having drug-resistant TB, from case detection to cure or, when a cure cannot
be achieved, through end-of-life care — an aspect of care which has been overlooked by TB control programmes and clinical research.

It is the fourth in a series of articles looking at the management of multi-drug resistant TB in the community. Previous articles covered the epidemiology and implications of MDR-TB in people with HIV (HATIP 162); how to improve diagnosis and case detection (HATIP 164), and models of MDR-TB care delivery in community settings (HATIP 165).

This HATIP describes
the sequence of care, and highlights some of the key messages, challenges and controversies
in care as described at recent conferences, discussions with our panel of
experts and during site visits in India and Khayelitsha, South Africa.

We hope to underscore
the importance of adopting a palliative care approach when working with
individuals and families affected by drug-resistant TB, often in the context of
HIV.

Why a palliative care approach to MDR-TB is necessary

“I’m still very much influenced by my
background as a doctor and clinician and so want to see we can support
countries and governments to care for people, not just cure pieces of lungs
that happen to be sick, but to look at the individual. It’s difficult to come
out with these ideas in an environment where things are so focused on outcomes,
how many people cured, how many DOTS programmes are [being created]. But how
about all the people, how about those that we are not curing? What are
we doing to provide for these people and families and relatives with decent
care — and not just delivering pills?”
Dr Ernesto Jaramillo of WHO’s STOP TB Department told HATIP.

This patient-centred approach — one that considers the physical,
emotional, psychosocial, material and spiritual needs individual with M/XDR-TB
and his or her family —could improve the health outcomes (and help TB
programmes reach their targets) whether the person is managed at a hospital, a
clinic, or in their home. But much more importantly, it should reduce suffering
and improve the quality of life for the affected family, regardless of the
outcome.

A palliative care patient-centred approach should be incorporated into
each step of care, from presentation through to end of life care. To support
the palliative care needs of people with M/XDR-TB, a number of resources are in
development, for instance, the Hospice
Palliative Care Association (HPCA) is in the process of finalising guidelines
for the provision of palliative care to patients with drug-resistant TB.

We should first start however by pointing out that the guidelines for M/XDR-TB
care are addressed by a number of WHO documents: the 2008 edition of the Guidelines for Programmatic Management
of Drug-Resistant TB (PMDT), and its accompanying Field
Guide on the Management of MDR-TB which are both soon to be updated. In addition, the 2010 Treatment of
Tuberculosis Guidelines contains some of key updates (such as a shift in
emphasis towards universal access to diagnosis and care).

As this HATIP goes to press, the best published resource on the
topic that we can identify is the Field Guide, authored by Dr Kwonjune Seung and
Dr Hind Satti of Partners in Health Lesotho.

This
article relies heavily on their guide, which follows the format of the Integrated
Management of Adolescent and Adult Illness (IMAI) module, describes how to
provide care and treatment at the primary care level. It recommends that
healthcare workers use
the general principles of good chronic care with their client:

We would urge you to download this
version of the field guide. Another version is in the works, which we
understand will contain more information than is currently in the Guidelines
for Programmatic Management of Drug-Resistant TB (PMDT), which will no doubt be
useful. However, the simplicity of the field guide makes it very handy for
nurses and other mid-level cadre health workers to use.

First contact, triage, and baseline assessments

The first contact with the
patient will differ somewhat depending upon how their case was identified and
the type of facility that initiates TB treatment. If only certain TB facilities
are managing MDR-TB cases, the patient will have to be traced and contacted in
order to be admitted into the programme, while programmes that have integrated
MDR-TB management into existing primary TB care clinics — such as in Khayelitsha
— will already have the client in care. Upon enrolment, some programmes assign
the patient to a nurse or community health worker, who becomes responsible for
contact, initial assessments and follow-up.

If the patient first comes
in to a clinic for care, the Field Guide recommends triage basics. After
receiving the client and retrieving their records, health staff should make
certain that smear-positive cases are instructed in cough hygiene, and to first
attend to new smear-positive MDR-TB cases (who are likely to be infectious
since they are not yet on effective treatment). The field guide recommends that
the facility should follow good infection control practice in the waiting areas
— isolating people with HIV away from smear-positive TB cases, and isolating
smear-positive MDR-TB cases from other TB cases.

It is notable that the
approach to separating clients due to HIV status and infectiousness is
different in some facilities, however. Since the most infectious TB cases and
most susceptible HIV patients are usually undiagnosed when they arrive at the
facility, some clinics have everyone wait in highly ventilated or
outdoor waiting areas — and to make certain that everyone wears surgical masks
and practices cough hygiene (as is done in the Ubuntu Clinic in Khayelitsha).

Furthermore, having
everyone wear a surgical mask may also be less stigmatising for the person
suspected of having drug-resistant TB. These waiting rooms are public places,
and different isolation policies for different individuals could mark them in
the community or potentially disclose their HIV status.

During the first meeting
with someone who has been newly diagnosed with drug-resistant TB, education and
adherence preparation are essential; baseline clinical and laboratory work should
be performed; and there should be an assessment of the family status and the
patient’s other psychosocial and socioeconomic circumstances.

Education and preparing for adherence

“Addressing
adherence is the key to success,” said Dr Hind Satti at the 40th Union World
Conference on Lung Health in Cancun. This is an understatement — and adherence
preparation is even more essential in a person with drug-resistant TB,
particularly for those who acquired drug resistance due to poor adherence. The
Field Guide suggests using the Five A’s, which we have abbreviated as follows:

Assessing the patient’s level of understanding about
TB, its treatment and drug resistance is the first step in the education and
adherence preparation process. Finding out whether the patient knows his or her
HIV status, and assessing their treatment history, ability to keep
appointments, and to adhere to other medications are also recommended.

It may be useful to have the
attending nurse fill out a questionnaire regarding the psychosocial and
socioeconomic circumstances of the patient as it can provide insight for the
community staff regarding what to expect when visiting the patient and their
family in the home.1

Advise: The health care worker should
explain key educational messages about drug-resistant TB, such as how it
evolves, how it is transmitted, and how people with HIV are more susceptible.
The patient should be told that he or she may be infectious, particularly while
smear-positive, and that he or she needs to be conscious of infection control
in the home and other areas (for instance, they should wear a surgical mask
when using, or avoid, public transport).

DR-TB treatment and its duration need
to be explained — including the fact that there is no other treatment. In
addition, the patient (and their treatment supporter at subsequent visits)
should be told about the side-effects of second-line TB treatment that can be
managed, if the patient and their treatment supporter communicate problems with
the DR clinical team.

Agree: The treatment partnership requires that the patients agree to take the full course of
treatment and to attend scheduled clinic visits. If care is clinic or
community-based, one of the first things to do is discuss with the patient and
agree with the patient on a treatment supporter (the health staff should be prepared to offer a list of possible
candidates who are willing and who live nearby).

Assist: The patient can be given advice to facilitate
adherence. They can also be put in contact with support groups and assisted
with accessing social grants, food or nutritional or transportation support if
needed and available. Those who live in especially remote areas may need
assistance relocating closer to the clinic.

Arrange: It the patient is receiving injections at
home, these should be arranged. Arrangements should also be made to educate the
treatment supporter, family, and to conduct contact screening and assess
infection control in the home.

A similar process could be used during subsequent
visits to monitor adherence, to determine if there is a problem and assess the
reasons for non-adherence. Is it due to side-effects or forgetfulness? Are
there problems with the treatment supporter? Are there financial, transport
problems or a lack of food? Are there problems at work? Is the patient seldom
at home and disorganised? Are there other medical problems or substance use
issues? Is the patient depressed? Key messages about treatment and adherence
can be reinforced as needed.

Staff should also assist the client with aids or
skills to improve adherence, and try to make sure that the patient has adequate
support by obtaining help from family and friends, working with the treatment
supporter to find solutions or referring them to a support group. Referrals can
also be made for members of the clinical team for medical or psychological
care, or arrangements made with a social worker or local NGO’s to help the
patient get needed socio-economic support.

Adherence support at TRC in India is individualised - and based on getting to know the patient

“MDR-TB patients are a difficult lot to deal with. We find many
of them just give up, are angry, feel hopeless. So we try to find what it is
that challenges them. But one thing which we try to contribute a lot is motivation,”
Dr Beena Thomas of the Tuberculosis Research Centre (TRC) in Chennai, India,
told HATIP.

The TRC runs many important TB clinical trials and maintains a
very high rate of adherence despite what are sometimes challenging protocols
for the patients. Part of this is due to careful patient selection, but Dr Thomas
explained that they spend time getting to know the patient. Then they use what
they have learned to work through whatever the barriers to adherence might be.

She explained that TRC is conducting a DOTS-plus MDR-TB study.
Upon diagnosis, treatment is begun almost immediately but the Centre encourages
the patients to be admitted to the hospital for two months, or “at least for 15
days until they feel that the client is okay with coming to take their
injections,” she said.

Dr Thomas described one case where a patient was threatening to
quit the study (and treatment). Quitting the study she said was one thing but
to quit treatment was another problem altogether.

“I had to sit with him for about an hour. His problem was [the
requirement] to take 24 months of treatment — that and his family. His whole
family has written him off as a diseased person. Because of the twenty-four
months of treatment [when they knew it normally took six months to treat TB],
they said ‘what’s wrong with you!` On
one hand, they are trying to be over-indulgent but at the same time they are
making the patient feel like he is the most useless human being on earth.
Everyone is telling him what to do. And his wife is getting upset.”

So Dr Thomas had to call various family members and speak to the
wife. “Then I explained to him
everything about his lab results, which is another thing which is hardly done —
how many people take time to explain to the patient their investigations, and
the research?”

“And I had to keep saying: ‘Forget you say you are hopeless, you
don’t want treatment, you’ve reached the end of your tether. You are
responsible for this lady here. So it’s not about you alone. You have to look
after yourself, get well, to look after her,’ — and they are married for hardly
two years. — ‘you need to start a family. Why do you make yourself feel like as
if you’ve got some terminal illness where you don’t — just because you have to
take 24 months? Just get on with it! And with some support of your wife, you
are going to really respond and then you know.’

“It was a ‘love-marriage’ [as opposed to an arranged marriage] so
I worked on that. I said, ‘What’s this romance about? Unless you get well, you
can throw romance out of the door and I said, ‘What about your sex life?’ So we
talked about that. So I said:
‘Hospitalised all the time? This is not fair to her. She left her family, she
had a tough time - all for you - and this is what you give her?’

“It took at least a couple of hours over a couple of visits with
them. But today that guy comes so regularly, and he
is doing so, so well.”

Dr Thomas clearly takes a somewhat aggressive approach to
adherence support, and it may not work for everyone or in every culture. But
the main point is that she gets to know the person and the family first before
she decides on an individualised intervention. And it is hard to argue with her
results — TRC studies have a very low rate of drop-outs and loss to follow-up.

Peer-delivered adherence support in Khayelitsha

Someone with personal experience taking a second-line regimen may
best be suited to follow-up on difficult patients. Busisiwe Beko is a former
MDR-TB patient, who supports adherence of people with MDR-TB in Khayelitsha. A
video shown at the 2nd South African TB Conference, followed Ms Beko
around on the job. After leaving the clinic, she spends most afternoons walking
the backstreets of Khayelitsha looking for defaulters, to stress the dangers of
not going back to treatment.

The video showed her approaching one woman who has become a
regular on her rounds.

"So what do you want to do? Nothing? You are not going for the
treatment?" said Ms Beko. "These drugs, if you are going to take them `on and
off, on and off` you are going to get resistance. And then from there you will
get extremely drug-resistant TB. So we have to stop the treatment until you
decide that you want to take the drugs. Please don’t do this."

However, at the conference,
an audience member noted that this sort of work can take a toll on peer
adherence supporters, who may need special psychosocial support and
training in order to keep working with sometimes very challenging cases.

Clinical and laboratory assessments

At the first visit, the
patient’s medical history should be reviewed, particularly their history of
past TB treatments. At each visit, the patient should be asked about their
general health, whether they have recently needed urgent medical care, and about TB symptoms and whether they have improved.

Once a person with MDR-TB
has started treatment, they should be asked carefully about side-effects such
as nausea/vomiting, fatigue, skin rash, tingling in hands or feet, deafness or
ringing of ears, headache, seizures or loss of consciousness, and whether
they’ve had feelings of anxiety, sadness or depression. Routine clinical assessments for weight loss, anaemia, jaundice and thrush
should also be performed.

Many programmes developed
standardised checklists to make certain that the patient is asked about each
important symptom at every follow-up visit. But it is particularly important to
know whether the patient is pregnant, has a liver problem, diabetes, heart or
kidney disease before starting a second-line TB regimen (pregnancy is not a
contraindication for MDR-TB treatment, but ethionamide and injectable TB drugs
should probably be avoided in pregnant women).

The Field Guide recommends
that before starting on second-line TB treatment, the patient should have a
complete blood count (CBC), and their aspartate transaminase (AST), alanaine
transaminase (ALT), bilirubin, creatinine, and potassium levels checked the first
few months, while thryroid-stimulating hormone levels should be checked at
month two and intermittently thereafter. Women should have a pregnancy test.
Provider-initiated HIV testing and counselling should be offered to all
patients whose HIV status is unknown. Those who are HIV-positive, should have a
CD4 cell count, and haemoglobin levels should be checked for any patient who is
beginning an AZT-containing ART regimen.

Schedule of lab work for
people with MDR-TB (adapted from the Field Guide on the Management of MDR-TB)

Month

Clinical
consult

Smear

Culture

DST

AST,
ALT, bili†

CR, K†

TSH

1

Every 2
weeks

√

√

√

2

√

√

√

√*

3

√

√

√

√

4

Monthly

√

5

√

6

√

√

√

√

7

√

8

√

9

√

√

10

√

11

√

12

√

√

√

√

Until
completion

Monthly

Every
three months

Every
six months

†
Liver function and renal function tests may be done at any time when clinically
indicated.

*
TSH in month two is recommended in settings with early onset of hypothyroidism.

Assessment of the family situation and infection control in the home

As already
noted, the patient should be asked about their family (including pregnancy
status in women, who should practice contraception while on MDR-TB treatment).
Immediately after admission into a community-based or clinic-based programme,
community workers/outreach staff should visit the home and screen all the
household contacts for HIV and TB.2
The visit also offers an opportunity to educate the family to support the
person with MDR-TB, and to assess and make recommendations for improving
infection control in the home.

“An
individual infection control plan is devised for each patient. Those who are
believed to be highly infectious are relocated to PIHL rental homes until they
are sputum culture-negative (thus avoiding hospital admission),” according to a
poster at the 2nd South African TB conference (2nd SATB).3

MSF’s approach to infection control in the home and community

“Most transmission probably occurs before diagnosis
and treatment initiation, and improving case detection and getting more
patients onto treatment earlier is key to reducing transmission,” Dr Helen Cox of MSF in Khayelitsha said at
the 2nd SATB conference earlier this year. “We have more than 60%
rate of culture conversion by two months of treatment in our programme, and
although we don’t really have a measure for infectiousness, in light of Dr Ed
Nardell’s research (see
previous HATIP), clearly infectiousness will have dropped rapidly
considering how quickly people are culture converting. So given the relative
proportion of patients who are undetected and undiagnosed, the risk of
infection is really there.”

“Consistently, however, there are around 10% of patients who
have not culture converted by six months of treatment, and these are very
important patients, because they will still be infectious and they will still
be in their homes. So I think it emphasises the importance of proper monitoring
and monthly cultures and actually identifying these patients so that we take
extra measures such as changing their treatment, hospitalising them or taking
extra infection control measures in the home,” she said.

To assess and improve infection control in the home, a
counsellor visits each household, to educate the patient and family members, to
talk about TB transmission, what is this disease, how does the treatment work,
etc. But included in the visit is an assessment of the vulnerability of that
particular household when it comes to TB transmission risk — how overcrowded is
the home, does it contain people who are HIV-positive, are there very young
children, are there concomitant illnesses?.

From this visit, a risk reduction plan is formulated
specifically for that household. Dr Cox said that a “major part of it is
education about TB transmission and cough hygiene — together with separate
sleeping arrangements. The patient is also encouraged to wear a paper mask in
overcrowded and closed conditions, and the caregiver is provided with N95
respirators. We also provide follow-up and support.”

But Dr Cox didn’t place that much emphasis on ventilation.
“It’s very hard to keep windows open, there are security issues and it’s cold —
so it is something that, in practical
terms, is not that easy to do,” she said. She added that although they haven’t
performed a formal evaluation, they have observed that among 80 houses visited,
about 67 were able to make arrangements for the patient to sleep alone. Some
additional shacks have been provided, and there have been some cases where they
decided that they needed to admit patients for infection control-related
reasons.

Treatment: empiric treatment and optimising regimens

Once
adherence preparation has been completed, it is important to get someone on an
effective regimen as quickly as possible. But knowledge of what regimen to use
— or even who to treat — is limited by lab capacity.

HATIP
164 described how most countries do not yet have access to rapid drug
sensitivity testing, and as a site visit to Khayelitsha demonstrated, even when the new tests are being rolled out, it takes a while to
use them to their full potential in the clinic (at present rapid DST is only
being conducted on cultures). In other words, it can take at least one month to
confirm drug-resistant TB in suspected cases, and the process takes longer when
rapid drug susceptibility testing is only performed after documented treatment
failures.

In the
meantime, clinical decisions need to be made about how to treat people at risk
of resistance — keeping in mind that people with HIV in particular, may not survive
long on ineffective first-line treatment. In some cases, empiric treatment for
drug-resistant TB may be warranted — but there are few clinical data, and
opinions vary widely on the subject.

In Lesotho (and in the Field Guide), the
following protocol is recommended for empiric treatment.

Whenever anyone is categorised as being at
medium or high risk of DR-TB (based upon their treatment and contact history),
two sputums are sent out for culture and DST.

The initial treatment while waiting for the DST
results depends upon catagorisation by risk of resistance. Migrants and health
workers with TB are categorised as being at risk for DR-TB but are placed upon
a first-line regimen until DST results come back indicating the need for second
line treatment.

Previously treated patients who have defaulted
or relapsed are placed upon what was once called the ‘category II regimen’ or
now, the retreatment regimen (a slightly prolonged and beefed up version of the
standard regimen with streptomycin thrown in). WHO wants to move away from the
retreatment regimen as rapid DST becomes more widely available, because it is
not effective against drug-resistant TB and it is unnecessary for drug-susceptible
TB.

People with active TB who are household
contacts of a person with M/XDR-TB are placed upon the same second-line TB
treatment that their contact is taking. For anyone with a history of treatment
with second-line drugs, a specialist is consulted to help construct an
individualised regimen (avoiding previously used drugs if possible). Probable
treatment failures, including anyone who is smear-positive in the fifth month
of the first-line or re-treatment regimen, or people with HIV who worsen on treatment,
start with a standardised second-line treatment regimen. But, the Field Guide
notes: “there are many reasons for clinical worsening in HIV-positive patients
besides treatment failure. Consult specialist for advice."

Dr Hind Satti insisted that, in Lesotho at
least, “We find
empiric treatment of MDR-TB suspects is very helpful in decreasing early
mortality of these patients and this is why we worked out the protocol for medium
and high-risk patients.”

In other settings, though, clinicians are likely to
wait for more laboratory or clinical confirmation of failure on first-line
treatment. During a visit to the Ubuntu clinic in Khayelitsha, we learnt that
if a household contact of a person with M/XDR-TB develops active disease, the
care team doesn’t immediately put the person on the same treatment as the index
case, because they have found that in most of the cases, the person will have
drug-susceptible TB (which is really ubiquitous in this setting). However, they
will send out for a rapid DST and switch treatment if necessary based upon
those results. And according to Dr Simiso Sokhela, a clinical officer at the site, they still commonly use the retreatment regimen.

“The few cases that have
had empiric TB treatment, it will be discussed and started on by
specialists. We can’t do it on a clinic basis. We have to refer to somebody else to make the
decision to start on empiric MDR-TB treatment.
But the best that we can do is the retreatment regimen, which is just adding one drug to a failing regimen,” she said.

“We do have to be careful about starting patients on empiric
treatment for failure,” Dr Helen Cox said. “Because in Dr Graeme Meintjes and
Dominique Pepper’s study on deterioration on TB treatment, drug-resistant TB
is only a small fraction of that. There are all of these other reasons for
failure.”

Indeed, in the study by Pepper et al in people with
HIV and TB on dual treatment, only 10% of the clinical deterioration that
occurred was due to drug-resistant TB, while 72% was due to other illness, most
commonly other AIDS-defining events. TB Immune Reconstitution Inflammatory
Syndrome was a greater cause of illness than MDR-TB (18%). 4

Dr Graeme Meintjes of GF Jooste Hospital explained
his view on the matter to HATIP.

“Regarding the decision to start empiric MDR
treatment in a patient suspected of having MDR TB before lab confirmation, there
is no clinical data on this that I am aware of. My view is that this should
only be done in exceptional circumstances given the toxicities, duration, cost
and poorer efficacy of MDR-TB treatment. The latter consideration is important
because starting a patient with susceptible TB on MDR treatment is doing them a
major disservice. My approach is to only consider MDR-TB treatment empirically
in the following circumstance:

•
The patient is hospitalised

•
The original diagnosis of TB is proven by smear or
culture

•
Other causes for deterioration have been excluded

•
The patient is deteriorating with features of TB
despite adherence to TB treatment

•
If this patient had MDR-TB and I don’t start MDR-TB
treatment they are likely to die within the next 2-3 weeks (respiratory
distress, severe wasting syndrome, neuroTB, etc)

•
That several clinical specimens have been sent for
culture and DST

•
Then start 3 MDR-TB drugs in addition to Rifafour while awaiting the DST result

•
Follow up clinical and lab results closely”

Only a minority of patients who deteriorate have MDR. This is relevant
to the decision.”

The starting second-line regimen can vary from place to place — in Nepal
for instance, the standardised regimen has been selected upon the basis of
resistance surveillance studies of the population — and according to the recent
paper by Malla et al, this was simpler for supply logistics and for providing
standardised training to health personnel.5
In other settings, programmes use a broad standardised regimen with the goal of
having several active drugs, which might be modified based on treatment or
contact history, and then modified again on the basis of DST results once they
become available.

The TB Treatment Guidelines state that treatment regimens should consist
of at least four drugs with either certain, or almost certain, effectiveness,
including whatever first-line drugs to which the individual may still be
susceptible to. If the effectiveness of a certain drug is not clear (and for
some drugs, this may be because DST results are less reliable), the drug may be
used, but it should not be depended upon as one of the four drugs. Group 5
drugs are generally reserved for XDR-TB regimens (and to some extent, are only
used because it is difficult to come up with any other options). More detailed
information on each drug, including adverse effects, contraindications,
monitoring, and dosing based on weight bands is available in the annexes of the
Treatment of Tuberculosis Guidelines (4th Edition).

Treatment is generally given in an intense phase (with more drugs) for
at least six months (Nepal treats intensely for eight months) followed by a
less intense phase of 12-18 months (usually without the injectable drugs).

Optimising the regimen in Khayelitsha

“We need a regimen that requires minimal adjustment once we
have DST available, because otherwise, we risk losing the drugs that we are
using at that point of time,” Dr
Helen Cox said during yet another presentation at the 2nd SATB
Conference titled “One chance of cure and the need for a strengthened starting regimen
in South Africa.”

At present, South Africa’s
standard starting regimen is kanamycin, ofloxacin, ethambutol,
pyrazinamide, ethionamide and terizidone
(which has only recently been
added). But Dr Cox walked the audience through a case study to illustrate some of the common problems with
this regimen.

In the case study rapid DST results have shown that the patient is resistant to
isoniazid and rifampicin. When the culture DST results come back, they indicate
that the person is resistant to ethambutol and ofloxacin. Unfortunately, DST
isn’t reliable when it comes to pyrazinamide or ethionamide, so “we have got
two drugs in the regimen that may be working for this particular patient. While we have a lower risk of
developing XDR-TB [than when terizidone wasn’t in the regimen], I’m sure
most of you who are treating DR-TB would not rely on just two drugs in the regimen - it’s not going to be effective at all,” Dr Cox
said.

At MSF, they have decided to
replace ofloxacin with moxifloxacin, which data seem to suggest may be
effective against some ofloxacin resistant strains. "[And when the DST results come in] we can also add further drugs like
PAS at this point, because we not actually adding a drug to a failing regimen.
Hopefully, at this point we’ve had three drugs on board that are working and
it’s not going to fail. So we have a much lower risk of XDR-TB developing,” said Dr Cox.

But there is a problem with this approach. MSF is currently
supplying the drug on a pilot basis in Khayelitsha — no one else can afford it.
“Moxifloxacin is currently incredibly expensive and very few national
programmes - including South Africa - can afford to purchase this drug at this
current point of time. And it’s certainly not something that we would expect
until the price comes down. So we need
much more advocacy to reduce the price and increase access to moxifloxacin. And certainly MSF internationally is working
on this because we feel that this is a key drug for DR-TB, that people who have
DR-TB should have access to,” she said.

In the meantime, South Africa is considering replacing ofloxacin
with high dose levofloxacin, which may also retain some activity against
ofloxacin-resistant TB.

In fact, in a review of the second-line drugs given at the Union World Conference on Lung Health in Cancun last
year, Dr Salmaan Keshavjee, or Harvard University and the Green Light Committee
noted “there may be things about these fluoroquinalones and the way that
they’re working that we’re not fully knowledgeable on yet.”

MDR-TB palliative care in children

A couple years ago, HATIP
published a clinical review series on TB in children. One of the cases cited in
the series concerned a child with XDR-TB that failed to respond to any
treatment. But as Dr Diana Gibb, of the UK's Medical Research Council Clinical Trials Unit pointed out to HATIP, the diagnosis,
care and management of children suspected of having MDR-TB, XDR-TB is extremely
difficult.

“Diagnosis of children with
MDR or XDR TB is very difficult as we know,” she said. “For instance, it is
very difficult to get a sputum specimen from a child - and without sputum, it
is difficult to get culture or DST. Thus detecting resistance has to be done
almost by proxy - in other words, if a household adult has MDR or XDR. And then
what about treatment? It’s going very slowly for kids.”

Commonly, children with TB
who are household contacts of a person with M/XDR-TB are treated with the same
drugs as are used in their parents. However, Dr Tony Moll, describing contact
tracing in the community at the Union World Conference on Lung Health in Paris in 2008, noted that
most of the child household contacts of XDR-TB patients that they identified
appeared to have drug-susceptible disease, or to at least respond to standard
treatment.

In Khayelitsha, however,
some children are being managed as though they have drug-resistant TB.
According to Dr Cox, they consult with a specialist, who "looks at how
close the index case is to the child and the age of the child, and makes an
assessment on that. Obviously, the risk of drug resistance is high, if the
child is being breastfed by the index case, who’s smear-positive drug-resistant
TB.

"The decision on what
to use for treatment is based upon the proximity of the contact," said Dr
Sokhela, "but we've had a few children who've had no TB contact in the
house at all. So we do know they have contacts elsewhere. But at the same time,
just because there's an active M/XDR-TB case in the house, doesn't mean they
might not have another contact elsewhere with drug-susceptible TB."

Dr Joan Marston of the
Hospice Palliative Care Association of South Africa told HATIP that these
children have special palliative care needs: “What we are seeing in children’s
palliative care is that children are admitted with drug-resistant TB, often for
periods of up to two years, and need to have special schooling in hospital,
where this is available.

“Often for financial
reasons, families cannot visit regularly and the contact between the child and
family is broken. I have seen children suffering from depression due to the
separation and families eventually abandoning the child. Childrens’ hospices
may then admit children who are smear-negative for completion of treatment and
are then faced with the problem of re-integrating children into their families
or finding alternative care. Children need intensive support through this
period and after they leave hospital after they are reintegrated.”

HIV care in people with MDR-TB

A number of studies appear to indicate improved
outcomes even of XDR-TB in people who are on antiretroviral therapy; and it is
WHO policy to initiate ART treatment as soon as feasible in people who are
coinfected with TB and HIV. Likewise, cotrimoxazole prophylaxis should be given
to all TB patients with HIV. However, as
in TB programmes in general, this will require very strong linkages between
DR-TB care delivery sites or complete `one-stop` service integration to get people
with drug-resistant TB onto ART in a timely fashion. Clinicians should be on
the alert for TB-IRIS however.

Manage common clinical problems

Palliative care looks beyond simply treating the
pathogen, but strives to relieve the symptoms and suffering associated with the
illness. The following section is abbreviated from the Field Guide.

Cough or difficult breathing: TB causes cough that
may take several months to resolve despite effective TB treatment, and in some
cases scarring of the lungs can lead to worsening wheezing. In addition,
secondary bronchitis or pneumonia can occur. In people with HIV, Pnuemocystis jirovecii pneumonia (PCP)
may need to be considered. In people who have recently started ART, a worsening
cough may be a sign of TB IRIS. If difficulty breathing is associated with
nausea and abdominal pain in someone taking d4T, it may be a sign of lactic
acidosis. A
beta-agonist inhaler may relieve coughing and wheezing. When there is severe
shortness of breath, a short course of prednisone (10-20 mg) daily for seven
days may be considered.

Haemoptysis (coughing up blood): Chronic haemoptysis
with small amounts of blood is common and may take months to resolve on
effective TB treatment, but can be dangerous and life-threatening if there is a
large volume of blood. Call a specialist.

Persistent fever: TB-related fever may take months
to resolve. Other fevers could be due to other common causes or TB IRIS.
Supportive care includes increased fluid intake to prevent dehydration,
moderate doses of paracetamol, and sponging with tepid water if the patient
wishes.

Persistent nausea or vomiting: A number of the
second-line TB drugs can cause persistent nausea or vomiting, usually
ethionamide (more immediate) or PAS (more delayed). The effect is dose-related
but reducing the dose may lead to treatment failure, so consult for advice. Antiretroviral
drugs such as AZT can cause transient nausea; if associated with d4T and
shortness of breath it may be a sign of lactic acidosis.

Supportive care: It is important to encourage
the patient to keep taking treatment — gastrointestinal side-effects are a
leading cause of treatment discontinuation, and are worse at the start of
treatment. Staggering the doses so the patient does not have to take all drugs
at once and giving soft porridge before taking the doses may reduce nausea.
Increase fluid intake to prevent dehydration, with non-caffeinated,
non-alcoholic drinks. Give metoclopramide (10 mg every eight hours, or 30-60
minutes before doses).

Persistent diarrhoea: Persistent diarrhoea may be caused by PAS but in
people with HIV, there may be an infectious cause that should be treated it
empirically. Supportive care includes increasing the patient’s fluid intake to
prevent dehydration. Give oral rehydration salts if there is a large volume of
diarrhoea. If the diarrhoea is drug-related, consider a constipating drug
unless there is blood in the stool or fever is present or if the patient is
elderly. Advise the patient on care for their rectal area and a supportive
diet.

Peripheral
neuropathy: Many TB and HIV drugs can cause peripheral neuropathy
that can result in permanent nerve damage. If d4T is causing neuropathy, switch to tenofovir or
AZT. If cycloserine/terizidone or an injectable is causing neuropathy, discuss
the risks and benefits of decreasing the dose or stopping these drugs — one of
the risks is treatment failure. Supportive care: make sure the patient is
taking pyridoxine. See HATIP 133 on peripheral neuropathy.

Depression, anxiety or psychosis: Depression and anxiety can be caused by many things
in people with drug resistant TB, including socioeconomic problems. In people
with HIV, it is sometimes associated with efavirenz. However, terizidone or cycloserine can cause severe
depression, anxiety or psychosis and can even lead to coma. Symptoms usually
improve when the dose of cycloserine is decreased. Stop cycloserine immediately
if the patient is suicidal or psychotic.

Hypokalaemia (low potassium): Low potassium levels are common in severely ill
patients and may be caused by a variety of things including vomiting, diarrhoea,
drugs and other reasons. It may present with symptoms such as fatigue, cramps,
numbness, paraesthesias, leg weakness, palpitations, somnolence, and confusion.
The injectable drugs, particularly capreomycin, can cause hypokalaemia due to
its effects on the kidney. Potassium should be checked on a regular basis
whenever beginning to use an injectable. Management: give the patient oral
potassium and magnesium supplements, and check the potassium in a few days. In
severe cases, intravenous replacement is needed. Call for advice.

Managing the side-effects of drugs

A table in the Field Guide provides a good overview of the side-effects
of second-line TB medications. At recent meetings the extremely high rate of adverse
events seen with these drugs has also been discussed extensively. According to Dr
Satti, the rates appear higher in southern Africa.

“For inpatients we usually admit very sick patients mostly co-infected, they are bedridden
and severely wasted with severe opportunistic infections or patients who
develop severe side-effects, among them liver toxicity [severe hypokalemia] and
acute renal failure,” she said. “We’ve tried to compare what side-effects that
we are seeing in our patients with those happening in the rest of the
countries. And it was very interesting to see a big, huge difference between
the percentage of side-effects that we are observing among our patients and
what the community is reporting from other countries. Is it related to
HIV-infection? Or is it related to severe malnutrition that we are observing
among our patients?”

At the 2nd SATB Conference, Karen Shean of the Lung
Infection and Immunology Unit of the University of Cape Town reported similar
findings in South Africa.

“We know that drugs are poorly tolerated but we have few data,
especially in low-income countries, about severity of side-effects and tolerability of drugs,
specifically second-line drugs,” she said.

“We do know however that from a study done on defaulters on patient-related
reasons as to why they interrupted treatment, the highest cause was side-effects.
So we know we have a problem. But what is the effect of HIV infection on
treatment and adverse side-effects? How
does it affect tolerability and severity?”

Ms Shean, who is a nurse,
conducted a retrospective review of 115 XDR-TB cases from Upington, Cape
Town and Johannesburg looking at how XDR-TB regimens were tolerated, whether
people with HIV had more severe side-effects and how the adverse events
affected outcomes. Sixty-seven of the 115 (58%) reported adverse events.

Drugs used in regimens (n=115) and the severity of the events

Drug

Number of events (% of severe events)

Ethambutol

19 (41%)

Pyrazinamide

24 (30%)

Amoxicillin-clavulanate

19 (29%)

Dapsone

9 (25%)

Capreomycin

26 (25%)

Clarithromycin

23 (23%)

Terizidone

25 (24%)

Ethionamide

21 (24%)

PAS

24 (24%)

Ofloxacin

6 (21%)

INH

5 (13%)

20% of the cases, or one in five, had a severe side-effect —
severe enough for the drug to be stopped, to be life threatening or even cause
death (which occurred in 6 patients or 3.7%).

The most common side effects (n=161)

Side-effect

HIV-positive

HIV-negative

nausea and/or vomiting

17 (46%)

20 (54%)

diarrhoea

8 (36%)

14 (64%)

other GI symptoms

5 (25%)

15 (75%)

dizziness

5 (33%)

10 (67%)

hearing loss

2 (20%)

8 (80%)

renal failure

6 (60%)

4 (40%)

body aches/cramps

5 (50%)

5 (50%)

headache

4 (50%)

4 (50%)

skin reaction

4 (57%)

3 (43%)

hypokalemia

5 (71%)

2 (29%)

Women
were significantly more likely to experience severe ADRs (p=0.014) as were people with HIV (p=0.045).In addition those with severe ADRs
have poorer treatment related outcomes, with a lower sputum culture conversion
rate and a higher mortality rate.

“Early detection and monitoring of ADRs is crucial. All levels of
healthcare workers need to know the side-effects of their drugs, and I’m afraid
we fall down very badly on that. Unless we have early ‘picking-up’ or
monitoring and finding of these side-effects and early management of these
side-effects, we are losing patients. Not only to interruption but also to very
severe side-effects,” Shean said.

Peer support

There was considerable discussion of how to manage these side
effects at the 2nd South African TB Conference. One member of the
audience asked whether people were really experiencing the symptoms or whether
they had simply heard and were afraid of the symptoms — pre-emptively
complaining.

“The patients have a very good idea about which drug is causing
their side-effect. And sometimes when you see a doctor stopping 3 or 4 drugs
and then reintroducing and stopping this and starting that, you often wonder
why they don’t ask the patient, because the patients know very well. Even children can
identify which tablet is causing the problem,” she said.

“But the downside of
that, is that they tell each other. Often they spread that perception around
and you find in one ward that a whole lot of patients will be refusing
treatment. I think these kind of things really need to be explored. Is he now
stopping it because he knows it’s causing him gastric problems? Or is it
because the mate next door to him has said, `I’m not taking it! I wouldn’t take
it if I were you.`

Dr Helen Cox pointed out that they had observed this in
Khayelitsha. “What we found in Khayelitsha is we have these support groups in
all of the clinics that meet once a week; and they are structured and there’s a
counsellor there. And the patients themselves will talk about their
side-effects with the counsellor there who knows all about them. So you can
remove these sort of negative impacts of patients talking to each other with
some proper advice there. And then they
can help each other to get through the side-effects and stay on treatment. I
think having peer support is a very important thing for that,” she said.

Hearing loss

Others
wondered how to manage hearing loss associated with some second-line drugs when it starts occurring.

“It is actually very difficult to know what to do, when you do
see hearing loss during treatment,” said Dr Cox.

“I think the approach is to be very individualised — so if a
patient is starting to develop hearing loss, and maybe they’ve been on
treatment for 4 or 5 months and they are doing well otherwise, then you could
perhaps stop the injectable drug at that point. But if it’s very early on in
treatment, in the first month when you start to see this hearing loss, it’s
very difficult to know what to do because the injectable, as we know, is one of
the key drugs for DR-TB treatment. And there’s no evidence that reducing down
to three times a week actually makes much difference. Although some people are
doing this. We really need much more
data to be able to identify patients who might be liable to have hearing loss
during treatment. And we’re starting to do a study to follow this much more
closely.”

“I think we have all heard the expression - and it’s a very
brutal one - `deaf or dead?` And basically a lot of the time it comes down to
that,” said Ms Shean, adding that this was frequently a source of tension
between the audiologist and the doctor, who would insist ‘we need the
aminoglycoside.’

But especially if they are out-patients, watch your patients: How are they looking at you? Are they turning
their head sideways? Are they
complaining about noise in their ears? How
are your patients communicating? How deaf are they? I’m not saying that you shouldn’t stop, and
let everyone go deaf because that’s not good. But there are things we can do, not
just to stop immediately when the audiograms say stop. I think we have to have
a balance of what we do with patients - we need the aminoglycosides.”

“There’s an NGO which is selling secondhand hearing aids and
providing very good support services in terms of counselling but then also
provision of hearing aids. And so we are trying to link up with them so that
patients who do have hearing loss can actually access hearing aids,” said Dr
Gilles Van Cutsem during HATIP's site visit at the Ubuntu clinic. [The NGO in
question is Deaf Community of Cape Town — and anyone in the area who is
interested in the service should contact HATIP.]

Aside from hearing loss, Dr Sokhela told HATIP she gets the most
complaints about “GI symptoms, nausea, gastric pain. I think they complain more
about it because they’re more uncomfortable. I’m not even sure whether it’s the
one that they suffer from the most but it’s the one that they present with.
Because it makes you very uncomfortable.”

“I think this is the one that probably has the most impact on
adherence,” said Dr Cox.

“Because if you’re feeling nausea you won’t really take drugs,”
said Dr Sokhela. “But half the patients don’t know their kidneys are failing so
they will still come and get drugs. Which is why they have to monitor them
closely, do the bloods, the creatinine more often, potassium if they are on
capreomycin. But they will present
with GI symptoms and if you don’t sort them out, they stop taking the drugs.”

“So we use the adjunctive medicines to manage that. Sometimes you
have to change drugs or alter doses, split the ethionamide because the patient
doesn’t want to take [any] drugs no more.
But half the time they do well with just drugs to manage that,” she said.

Improving side-effect management is high on the
list of things to strengthen in the next version of WHO’s PMDT guidelines,
according to Dr Dennis Falzon.

“One of the questions we will look at is the toxicity
of drugs for MDR-TB among HIV infected patients, " he told HATIP. "We want to focus on the
surveillance of side-effects of TB drugs, particularly in patients with DR-TB
or HIV/TB or both. Better information will give us a handle on what is the
contribution of drug toxicity to poor adherence or other unfavourable outcomes.
The wider availability of drugs (possibly free-of-charge to the patient) to
provide symptomatic relief will be one thing to lobby for.”

The surveillance
of side-effects of drugs is done both routinely as well as actively. The
intention is to establish minimum requirements for pharmacovigilance (PV) for
all countries submitting proposals for TB funds to the GF. We are currently
working on a handbook not very different from the one already established for
ARVs,” he told HATIP.

Failing on treatment: options, clinical and palliative

But putting up
with poorly tolerated drugs is one thing is a cure is likely or possible.
However, as researchers from St Luke’s Hospice pointed out in a poster at the 2nd
SATB Conference, in many XDR-TB cases or cases where there are terminal
comorbid conditions, the patient may not be curable. A major issue is that
health care workers find it difficult to declare TB treatment futile because of
the infectious risk to society and because it is perceived as giving up on the
patient.

But it is important to not shy away from the
fact that M/XDR-TB is often a fatal disease. There may be some natural
reluctance to deal with this aspect of the clinical care of people with MDR-TB because
the media has so hyped M/XDR-TB as a ‘killer’ disease — and people may need to
be convinced that a cure is possible, in order to encourage them to adhere to
treatment.

But an unfortunate consequence for some people
is that their clinicians may keep force-feeding the patient drugs that are
doing nothing but increasing morbidity. There has been little to no research on
how to relieve suffering when TB has become a terminal condition, and one which
can take a long time to kill some individuals.

In addition, programmes are often at a loss of
where to send those deemed to be untreatable.

“It is an extremely complex problem,” said Dr Van Cutsem in
Khayelitsha. “Because at the moment there is this protocol that they need to be
discharged to their home with a lot of interventions to minimise the
risk of transmission at home. But the reality is that they’re
under-resourced so it doesn’t really happen in the way it is put in the protocol
and patients just sometimes [don’t bother to wear their masks]. And they are not
always so sick and can live for a few years with highly infectious XDR-TB. So at the moment we support the home - we try
- with the existing capacity. But we’ve also realised the limitations of that
strategy, or the risks of that strategy.

In other rare cases, programmes are being
confronted with difficult ethical decisions of whether to discontinue treatment
in people who repeatedly default on treatment.

“We have these hardcore group of people…. that are very difficult
to manage,” said Dr Keertan Dheda at the 2nd SATB Conference. “And
in the Western Cape we have a Review Committee that looks at these recurrent
defaulters. And we look at each case on its merits but there have been several
cases now where the Review Committee has taken a decision and actually
withdrawn further treatment. Because we felt that these patients were going to
default again and there was a high risk of amplifying resistance in these
patients.”

“And there’s this whole discussion on incarceration versus
confinement and there are these hardcore patients who simply will not take
their medications, will repeatedly come into hospital for short periods of time
and then default. How do we deal with this problem? Should we go back to the
old-style sanatoria? Should we have some incarceration facility, should we have
community treatment facilities?... Currently our XDR-TB beds in many of the
provinces are full. In fact in the Western Cape, we are now discharging failed XDR
treatment cases back into the community. Fair enough, we do an assessment of
the household, but it starts becoming very questionable when you start to
discharge patients into communities like this,” he said.

So now the Western Cape, which in other contexts,
is decentralising drug-resistant TB care to bring it closer to where people
live, plans to ship people who have failed XDR-TB care to a facility in
Nelspoort, a remote part of the province. This may simply be a matter of
convenience for the province, because the facility is available. But even so,
it's a six or seven hour drive away from where most of their families
live.

Again, responding to end-of-life issues seems
to be a blind spot in TB programmes, according to Dr Jaramillo of WHO.

“The issue of
palliative care in TB has been quite painful to me for a long time, and I’ve
felt quite lonely in that. Many people in TB simply didn’t care, or even felt
that paying attention to palliative care could be a distraction from delivering
treatment… We are using this figure, mostly for advocacy purposes, that 1.8
million people are dying of TB. This is awful, but what are we doing to provide
these people with a decent, dignified death?”

Indeed, although people with HIV have been
reported to die quite quickly from XDR-TB, it is not the case for many HIV-negative
people. We may also find that people on antiretrovirals may have prolonged slow
deaths from XDR-TB.

They will need compassionate end-of-life
care, but because this is a place where TB experts have refused to look, there
has been very little research on the subject. Dr Jaramillo told HATIP that
symptomatic relief for end-stage TB might be similar to that for chronic
obstructive pulmonary disorder (COPD). Palliative care for COPD is also relatively
neglected compared to, say, palliative care for lung cancer, the few palliative
care experts working with COPD patients are using respiratory-specific quality
of life symptom scales to assess their clients’ needs.

In assessments of
people with COPD, the symptom everyone said most impacted their quality of life
was dyspnoea — severe breathlessness (upon minor exertion or even while trying
to rest/sleep), and perhaps the anxiety associated with it.

The literature
suggests a number of supportive care interventions, including:

bronchodilators, especially long acting
ones;

opioids to treat dyspnoea — starting at
lower doses than used for pain control (1.25 or 2.5 mg orally every 4
hours, intermediate release methadone) and titrating up until symptomatic
improvement is obtained. (And it should of course be given with a
laxative);

benzodiazepines to reduce anxiety that can
accompany dyspnoea, and also to further reduce dyspnoea (midazolam);

potentially, oxygen therapy in settings
where this is available.

Dr Jaramillo and WHO plan to hold a consultation looking at palliative
care for drug-resistant TB in the near future. He told HATIP that some
consensus may be needed for such questions as when to give up on curative
treatment (although many people present late and die quickly, others can take a
long time either to recover or pass). What is reasonable? Worsening disease?
Failure to achieve culture conversion by 10 months? And what should be done to
alleviate symptoms and provide end-of-life care for people with M/XDR-TB — in
way that is safe for the family and the healthcare providers? Programmes and
healthcare workers clearly need guidance on these issues, he said.

In the meantime,
other models should be explored for providing high quality end-of-life care.

“I think there is
a capacity for some of these patients to be at home, but I don’t think we’ve
yet got a model, I think it requires much more intensive counselling and
support than even MSF have been providing to date, in terms of home patients,”
Dr Cox told HATIP. “So I think we need options for these patients, some sort of
facility - you know – within the community. I think we need a mix of models.
But I also think we have to caution against having one model for everyone.
Because everyone is different. Some people will have enough household support
and the family will be very supportive. Others not and so you need something
different for those ones, and you need inpatient [certainly] right at the end
for some people.”

For
instance, there are beds for end-of-life care reserved in the small inpatient
clinic in Khayelitsha, and some hospices may be able to provide a similar
service that is closer to the community — and close to the emotional and
spiritual support that families can provide. However, if palliative care teams
are to become involved, to support families, palliative care organisations need
to be trained in infection control measures, both for hospices and homes. And
finally, Dr Jaramillo pointed out to HATIP, “we also need to remember that
caregivers of people dying with or from TB also need to be given psychosocial
support.”

References

[1] Nkuebe M. Home assessment in the management of MDR-TB/HIV
patients in Lesotho.
2nd South African TB Conference, Durban 2010.

[2] Nkuebe M.
Home assessment in the management of MDR-TB/HIV patients in Lesotho. 2nd
South African TB Conference, Durban 2010.

[3] ibid.

[4] Pepper
DJ et al. Clinical
deterioration during antitubercular treatment at a district hospital in South
Africa: the importance of drug resistance and AIDS-defining illnesses. PLoS ONE 4(2): e4520.
doi:10.1371/journal.pone.0004520, 2009.

[5] Malla P et
al.

HATIP #167, October 18th 2010

This content was checked for accuracy at the time it was written. It may have been superseded by more recent developments. NAM recommends checking whether this is the most current information when making decisions that may affect your health.

NAM’s information is intended to support, rather than replace, consultation with a healthcare professional. Talk to your doctor or another member of your healthcare team for advice tailored to your situation.

The Community Consensus Statement is a joint initiative of AVAC, EATG, MSMGF, GNP+, HIV i-Base, the International HIV/AIDS Alliance, ITPC and NAM/aidsmap

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This content was checked for accuracy at the time it was written. It may have been superseded by more recent developments. NAM recommends
checking whether this is the most current information when making decisions that may affect your health.

NAM’s information is intended to support, rather than replace, consultation with a healthcare professional. Talk to your doctor or another member
of your healthcare team for advice tailored to your situation.